Association of the ATP-Binding Cassette Transporter A1 R230C Variant With Early-Onset Type 2 Diabetes in a Mexican Population

Abstract

OBJECTIVE—The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 in pancreatic β-cell function was recently observed in the mouse model, we assessed the association of this variant with type 2 diabetes in this population. RESEARCH DESIGN AND METHODS—The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20–69 years (121 with onset ≤45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics. RESULTS—R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (11.4%) in the initial study group (OR 2.501; P = 0.001). After stratifying by age at diagnosis, the association was significant only in the early-onset group (age at diagnosis ≤45 years) (OR 3.776, P = 3.3 × 10−6). Both associations remained significant after adjusting for admixture (P = 0.0008 and P = 8.1 × 10−6, respectively). Similar trends were observed in the independent study group, and the combined analysis of both populations showed a highly significant association of the R230C variant with type 2 diabetes, particularly with that of early onset (P = 7.6 × 10−6 and 9.4 × 10−8, respectively). CONCLUSIONS—The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.

HDLs, Diabetes, and Metabolic Syndrome

“…This notion is also supported by studies in humans displaying altered HDL metabolism due to polymorphisms in the ApoA-I and ABCA1 genes that have been associated with increased risk of diabetes and impaired glucose uptake (Morcillo et al 2005;Villarreal-Molina et al 2008). Heterozygotes for rare mutations in the ABCA1 gene that profoundly decrease HDL-C levels were found to be less glucose tolerant than their unaffected relatives (Vergeer et al 2010).…”

Association of adenosine triphosphate-binding cassette transporter A1 gene polymorphism with lipid profiles and early-onset type 2 diabetes

“…Subjects carrying loss-of-function mutations in ABCA1 show impaired insulin secretion but not insulin resistance 34,35 . In our present study, a significant association was identified between polymorphisms within ABCA1 SNP 22 found that the ABCA1 R230C variant is associated with early-onset T2DM in the Mexican population. The maximum allele frequency of the R230C variant however is less than 5% for the population in our study.…”

“…All the selected SNPs were selected in previous studies and exhibit allele frequencies of more than 5% in the Han Chinese population 22,24 . Linkage disequilibrium (LD) was performed with HAPLOVIEW 4.1, and the result showed LD between rs2487039 and rs2230806 (r 2 = 0.97).…”

“…Several ABCA1 polymorphisms and mutations have been reported to decrease HDL cholesterol levels [16][17][18][19] , obesity 16 , and T2DM 20, 21 across multiple ethnic groups. In the Mexican population, subjects with the R230C polymorphism (rs9282541) in the ABCA1 gene have low HDL 19 , increased body mass 16 , elevated haemoglobin A 1c levels, reduced fasting insulin, and early-onset T2DM 22 .…”

Candidate Genes in Adult Elderly and Adult Intermeddle Diabetes

“…DM in older adults can be treated in a timely manner and even prevented in people who present certain polymorphisms that cause the development of diabetes mellitus by themselves or that are at risk factor for their development, such as the rs13266634 of the gene SLC30A8 or SNP rs64771077 from JMJD1C gene, which are by diabetes a protector factor. [39][40][41] …”